Response to sorafenib in cisplatin-resistant thymic carcinoma: a case report

Abstract

Platinum-based chemotherapy regimens are often recommended for patients with unresectable thymic carcinoma. In more than 60 cases, however, the systemic chemotherapy provides little benefit. In this report, we described a case of advanced KIT- and VEGF-positive thymic carcinoma with liver and lung metastasis. The patient, a 46-year-old man, exhibited a resistance to cisplatin-based chemotherapy, but responded to the treatment with sorafenib, a molecular target-based therapy. After 4 months of sorafenib therapy, his lung and liver metastases as well as the mediastinal tumor shrank dramatically. Moreover, the tumors showed stable disease for at least 9 months. To the best of our knowledge, it is the first report about a response of advanced thymic carcinoma to sorafenib. The preliminary study suggested that molecular target-based therapy could be an alternative treatment to those chemotherapy-refractory patients.

Molecular aspects of thymic carcinoma

“…This involvement in the development and progression of malignant tumors represents a target for antiangiogenic agents like bevacizumab [43]. Protein expression of VEGF has only rarely been described in thymic carcinomas [19,30,38,44]. VEGF expression was identified in 62.5% and 75% of cases in Tomita et al's [44] and Kaira et al's [38] studies, respectively and in a single case described by Li et al [30].…”

“…Overexpression of c-kit has also been demonstrated in thymic carcinomas. Collectively, the percentage of c-kit positive cases averages 62.8% [3,[13][14][15][16]21,[26][27][28][29][30][31][32]. Contrary to the relatively high protein expression however, c-kit mutation is a rare event in thymic carcinomas (<10%) [13,14,19,21,26,28,29,31].…”

Thymic epithelial tumours: from basic principles to individualised treatment strategies

“…Given the significantly highest frequency of KIT expression in thymic carcinoma, some authors proposed KIT as a diagnostic marker of carcinoma of thymic origin versus other origins in the setting of a mediastinal tumour [111]. Despite the high expression of KIT, KIT gene mutations are found in only 9% of thymic carcinomas (13 out of 128 collectively analysed) (table 6) [26,[112][113][114][115][116][117]. Clinically, KIT mutant thymic carcinomas then represent a small molecular subset of thymic tumours.…”

Unexpected Dramatic Response of Pretreated Invasive Thymic Malignancies on Pemetrexed-Case Report and Review of Current Treatment Modalities

“…However, there are limited data regarding the efficacy of angiogenesis inhibitors in thymic malignnancies. Sorafenib and sunitinib have not been studied in formal clinical trial settings, although case reports have described evidence of the activity of these agents in thymic carcinoma [12][13][14].  Thymic malignancies have shown c-KIT positivity by IHC in 73% to 86% of TCs.…”

“…Some targeted agents like multi-kinase inhibitors sunitinib or sorafenib have shown some activity in thymoma [12][13][14]. Molecular profiling is therefore promising and may hopefully herald a new treatment paradigm for thymic malignancies.…”